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Major Advances in Emerging Degrader Technologies.

Hang Luo¹, Li Wu^1,2, Yujian He¹

¹School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, China.

Frontiers in Cell and Developmental Biology

|July 11, 2022

Summary

Emerging proteolysis-targeting chimeras (PROTACs) offer new therapeutic paradigms by degrading disease proteins. This review categorizes novel PROTACs and alternative degrader technologies, providing insights for future drug development.

Keywords:

analogous PROTACs degrader technologies emerging PROTACs lysosomal degradation ubiquitin-proteasome system

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Area of Science:

Biochemistry
Molecular Biology
Medicinal Chemistry

Background:

Proteolysis-targeting chimeras (PROTACs) are gaining traction in academia and industry for their ability to degrade disease-causing proteins.
Traditional PROTACs have limitations, necessitating exploration of new design strategies and degrader technologies.

Purpose of the Study:

To categorize emerging PROTACs and alternative protein degrader technologies.
To emphasize molecular design strategies for novel PROTACs.
To provide perspectives on the development and concerns of various degrader technologies.

Main Methods:

Categorization of emerging PROTACs, including modified classical and atypical PROTACs (e.g., nucleic acid-based).
Summarization of alternative degrader technologies like lysosome-targeting chimeras (LYTACs) and macroautophagy degradation targeting chimeras (MADTACs).
Discussion of RNA degradation targeting strategies.

Main Results:

Emerging PROTACs encompass modified classical and novel structures like nucleic acid-based PROTACs.
Alternative degradation pathways beyond lysosomal targeting are explored through LYTACs and MADTACs.
RNA degradation presents a new therapeutic avenue.

Conclusions:

Novel PROTAC designs and alternative degrader technologies expand therapeutic options.
Understanding diverse degradation mechanisms is crucial for advancing degrader technologies.
This review offers a guide for the development of future protein and RNA degrader therapeutics.